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Updated: Jan 30, 2026

Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
Synthesis of 1,3-Bis-trifluoromethylated (Hetero)cyclohexane-2-carboxylates from Alkylidenemalononitriles
Morgane Mando1, Akash R Gogate1, Dylan J Smith1
1Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Abstract:
Reported herein is a method for the syn-selective 1,3-bis-trifluoromethylation of (hetero)cycloalkylidenemalononitriles. The malononitrile-containing intermediate can be readily converted into carboxylates (and derivatives thereof) by oxidative decyanation. The products of this two-step sequence are 1,3-bis-trifluoromethylated physicochemically altered analogues of common (hetero)cyclohexane carboxylates. This study includes optimization of the bis-trifluoromethylation reaction, scope studies, synthesis of various new bis-trifluoromethylated (hetero)cycloalkane carboxylates, representative transformations relevant to pharmaceutical synthesis, mechanistic studies, and some computational analyses of the newly accessible scaffolds.
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